Mechanisms of bone metastases of breast cancer
- 1Departments of Orthopaedic Surgery, Barton Research Institute, Center for Orthopaedic Research
2Physiology and Biophysics,
3Radiation Oncology,
4Breast Cancer Research Program
5Hematology and Oncology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA
- (Correspondence should be addressed to L J Suva; Email: suvalarryj{at}uams.edu)
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Figure 1
Schematic of tumor–bone marrow microenvironment interactions. Invading tumor cells secrete osteolytic factors that can directly and indirectly stimulate osteoclastic bone resorption, by multinucleated osteoclasts (shown as green cells). Indirect stimulation is primarily by up-regulation of RANK–RANKL signaling by osteoblasts (shown as cuboidal pale blue cells on bone surface) or by stimulation of host immune cells that can increase RANK–RANKL signaling and also negatively regulate tumor cells. Tumor cells also secrete factors that can activate other receptors on the osteoblast, leading to increased osteolysis. Tumors also secrete agents such as VEGF and PDGF that influence vessel formation, as well as agents that can alter platelet function, both of which support osteoclastogenesis and osteolysis. Tumor cells may also influence other bone marrow microenvironment cells, such as stromal cells, which can be induced to differentiate towards the adipogeneic lineage (white cell; red nuclei) or that can become osteoblasts or that can otherwise support osteoclast progression through interactions in the bone marrow niche. The overall integrated result of increased tumor burden in bone in the case of metastatic breast cancer is increased osteolysis.
- © 2009 Society for Endocrinology
